Deoxyuridine triphosphatase (hereinafter referred to as dUTPase (EC3.6.1.23) at times) is a preventive DNA repair enzyme. This enzyme specifically recognizes only deoxyuridine triphosphate, distinguishing from other triphosphates of natural nucleic acids, and hydrolyses the deoxyuridine triphosphate to deoxyuridine monophosphate and pyrophosphoric acid. dUTPase is known to be an essential enzyme for the survival of both prokaryotic and eukaryotic cells.
In malignant tumors, it is suggested that malignancy is associated with high expression level of dUTPase (Non Patent document 1 and 2). It has also been reported that a tumor in which expression of the enzyme has been accelerated shows resistance to chemotherapy (Non Patent document 3). Moreover, potentiation of anti-tumor effect of a thymidylate synthase inhibitor (hereinafter referred to as a TS inhibitor) was observed when the expression level of dUTPase is decreased using siRNA in cultured cancer cells (Non Patent document 4). These findings suggest that human dUTPase inhibitors could be useful chemical sensitizers of anti-tumor agents.